The consequences of exposures to bone-seeking radionuclides including plutonium, americium, radium and others are well recognized and of considerable public concern. Current protection models are based largely on statistical assumptions with only minimal biological or experimental data. While these models may be suitable for the setting of exposure limits, our goal is to continue to derive an experimentally based biokinetic-dosimetric model of radiation dose-tissue interactions that will be predictive of tumor occurrence, latency periods, location, and frequency. Using existing data and tissue archives, the following aims will be accomplished: l) Neutron Induced Autoradiography (NIAR) based image analysis methods will determine tissue compartments, cellular distributions and radiation doses with time after monomeric 239Pu exposures in beagle dogs. 2) Morphometric, and morphological methods will define the biology of the beagle osseous tissues in the same specimens used for 239Pu localization and dosimetric evaluations. 3) To establish the relative biological determinants of actinide distribution, incorporation and retention in skeletal tissues. These include the affinity ratios for Pu in cortical/trabecular bone; cancellous bone in fatty/red marrow sites; surface deposition on osteoblastic active/resting surfaces. 4) From information obtained from Aims 1-3 and combined with tumor information from previous lifespan studies, a predictive tumor model for the beagle dog will continue to be developed. Some emphasis will be placed on the determination of "tissue weighting factors" (e.g. skeletal endosteum vs. liver) and evaluation of a potential inverse dose rate effect. 5) The human biology component will be determined from the literature and from some human material in archive. The tissue characteristics of that are likely to be important in the predictive tumor model include distribution of red/fatty marrow with age, skeletal turnover and metabolism, and densities of putative target cells. 6) Human dosimetry information will mostly be predicted from the beagle model, but confirmationed by analysis of 239Pu in the human skeleton. NIAR analyses of bones from exposed humans will be done. The human samples are provided by the USTUR and some tissues may be obtained from heavily exposed humans in Russia (Mayak workers). 7) From the experimentally derived model for the beagle and from data developed for the human, a biologically-based "tumor predictive" model will be constructed for the human. These studies will provide new knowledge on the biological behavior of Pu and other bone-seekers and an improved capability to predict the risks of exposure.